Unsaturated alcohols formation

In allylic and other unsaturated alcohols, formation of an 0-H insertion product clearly dominates the cyclopropanation reaction,e.g. formation of 18 and 19. 

Most ring syntheses of this type are of modern origin. The cobalt or rhodium carbonyl catalyzed hydrocarboxylation of unsaturated alcohols, amines or amides provides access to tetrahydrofuranones, pyrrolidones or succinimides, although appreciable amounts of the corresponding six-membered heterocycle may also be formed (Scheme 55a) (73JOM(47)28l). Hydrocarboxylation of 4-pentyn-2-ol with nickel carbonyl yields 3-methylenetetrahy-drofuranone (Scheme 55b). Carbonylation of Schiff bases yields 2-arylphthalimidines (Scheme 55c). The hydroformylation of o-nitrostyrene, subsequent reduction of the nitro group and cyclization leads to the formation of skatole (Scheme 55d) (81CC82). 

The above methodology has been extremely useful for the synthesis of a variety of INOC precursors. For instance, treatment of 0-trimethylsilyl a-bro-moaldoximes 52b, e, f with F ion in presence of unsaturated alcohols 57 produces oximino ethers 58 which can be readily oxidized using NaOCl (Scheme 8) [29]. The transient nitrile oxide intermediates formed undergo spontaneous cyclization to fused isoxazolines 59. The preferred stereoisomer in the formation of the five-membered ring ethers is trans whereas in the six-membered ring ethers the cis isomer predominates (see Table 5). MM2 calculations helped rationalize the experimentally observed stereoselectivites (see Table 5). 

Using the above procedures, allyl a-azido alkyl ethers of type 281 were prepared by employing an unsaturated alcohol such as allyl alcohol [76] (Scheme 32). The reaction of an aldehyde with allyl alcohol and HN3 in a ratio of 1 3 9 carried out in the presence of TiCl4 as catalyst provided azido ethers 281, 283, and 285 in 70-90% yield. The ratio of reagents is critical to ensure a high yield of azido ether and to prevent formation of acetal and diazide side products [75]. Thermolysis of azido alkenes 281, 283, and 285 in benzene (the solvent of choice) for 6-20 h led to 2,5-dihydrooxazoles 282,284, and 286, respectively, in 66-90% yield. 

Ir catalysts supported on binary oxides of Ti/Si and Nb/Si were prepared and essayed for the hydrogenation of a,P-unsaturated aldehydes reactions. The results of characterization revealed that monolayers of Ti/Si and Nb/Si allow a high metal distribution with a small size crystallite of Ir. The activity test indicates that the catalytic activity of these solids is dependent on the dispersion obtained and acidity of the solids. For molecules with a ring plane such as furfural and ciimamaldehyde, the adsorption mode can iirfluence the obtained products. SMSI effect (evidenced for H2 chemisorption) favors the formation of unsaturated alcohol. 

Various electrophilic selenium reagents such as those described in Scheme 4.3 can be used. V-Phenylselenylphthalimide is an excellent reagent for this process and permits the formation of large ring lactones." The advantage of the reagent in this particular application is the low nucleophilicity of phthalimide, which does not compete with the remote internal nucleophile. The reaction of phenylselenenyl chloride or V-phenylselenenylphthalimide with unsaturated alcohols leads to formation of (3-phenylselenenyl ethers. 

The reductive demercuration was marred by the loss of about half of the peroxide due to competing deoxymercuration which afforded 4-cycloocten-l-ol. An additional complication was the formation of a small amount of trans-1,2-epoxy-cw-cyclooct-5-ene. The bicyclic peroxide 50 was readily separated from the unsaturated alcohol by silica chromatography, but complete removal of the epoxide was more difficult. Preservation of the peroxide linkage was markedly higher in the bromodemercuration. The diastereoisomeric dibromoperoxides 51 were separated by HPLC, although only one isomer was fully characterised. 

The cinnamaldehyde substrate (13) with the standard conditions for 22 h shows 70% conversion to a mixture of mainly (65%) the saturated alcohol (15), with 10% unsaturated alcohol (14), 15% hydrogenolysis product (4a), and 10% of other trace materials (eq. 6). Product profiles as a function of time have not been investigated, but formation of 4a again likely derives from a direct hydrogenolysis of 15. 

Reduced furans are formed in two types of oxypalladation processes on substrate a,ft- and y,<5-unsaturated alcohols. In an unusual reaction, allyl alcohol is converted into 4-methylenetetrahydrofurfuryl alcohol, among other products (Scheme 57)97 the formation of propene is thought to arise by reductive hydrogenolysis of allyl alcohol. 

A typical reaction is the formation of 2-substituted 3,6-divinyltetrahydro-pyranes (108) by the reaction of butadiene with aldehydes (97-100). In this reaction, unsaturated noncyclized alcohols 109 are also formed. The selectivity to the pyranes and alcohols can be controlled by the ratio of Pd and PPh3 in the catalyst system. When the ratio was higher than 3, pyranes were formed exclusively. On the other hand, with the lower ratio of Pd and PPh3, the unsaturated alcohols were formed as the main product. 

The catalytic RCM with 31 as substrate (Scheme 7) is significantly more facile when the reaction is carried out under an atmosphere of ethylene, presumably due to the formation of the more active Mo=CH2 system (see below for further details). Thus, after catalytic removal of the directing unit, the chiral unsaturated alcohol (S)-32,the formal product of an enantioselective addition of the Grignard reagent to unfunctionalized heterocycle 33, is obtained. An additional in-... 

The enantioselective reduction of unsaturated alcohol derivatives has been applied to the synthesis of several biologically active compounds (Scheme 24.12). Warfarin (123, R=H) is an important anticoagulant that is normally prescribed as the racemate, despite the enantiomers having dissimilar pharmacological profiles. One of the earliest reported uses of DuPhos was in the development of a chiral switch for this bioactive molecule, facilitating the preparation of (R)- and (S)-warfarin [184]. Although attempted reduction of the parent hydroxycoumarin 122 (R=H) led to formation of an unreactive cyclic hemiketal, hydrogenation of the sodium salt proceeded smoothly with Rh-Et-DuPhos in 86-89% ee. 

This finding is the consequence of the distribution of various ruthenium(II) hydrides in aqueous solutions as a function of pH [RuHCl(mtppms)3] is stable in acidic solutions, while under basic conditions the dominant species is [RuH2(mtppms)4] [10, 11]. A similar distribution of the Ru(II) hydrido-species as a function of the pH was observed with complexes of the related p-monosulfo-nated triphenylphosphine, ptpprns, too [116]. Nevertheless, the picture is even more complicated, since the unsaturated alcohol saturated aldehyde ratio depends also on the hydrogen pressure, and selective formation of the allylic alcohol product can be observed in acidic solutions (e.g., at pH 3) at elevated pressures of H2 (10-40 bar [117, 120]). (The effects of pH on the reaction rate of C = 0 hydrogenation were also studied in detail with the [IrCp (H20)3]2+ and [RuCpH(pta)2] catalyst precursors [118, 128].)... 

Adogen has been shown to be an excellent phase-transfer catalyst for the per-carbonate oxidation of alcohols to the corresponding carbonyl compounds [1]. Generally, unsaturated alcohols are oxidized more readily than the saturated alcohols. The reaction is more effective when a catalytic amount of potassium dichromate is also added to the reaction mixture [ 1 ] comparable results have been obtained by the addition of catalytic amounts of pyridinium dichromate [2], The course of the corresponding oxidation of a-substituted benzylic alcohols is controlled by the nature of the a-substituent and the organic solvent. In addition to the expected ketones, cleavage of the a-substituent can occur with the formation of benzaldehyde, benzoic acid and benzoate esters. The cleavage products predominate when acetonitrile is used as the solvent [3]. 

Highly regioselective cyclizations of 3,4-, 4,5- and 5,6-unsaturated alcohols to yield tetrahydrofuranols and tetrahydropyranols have been carried out with the TS-I-H2O2 system (this is a titanium silicate molecular sieve-H202 complex.) The reactions involve the intermediate formation of epoxides and their Ni ring opening. 

In a water/chlorobenzene biphasic system, reduction of aromatic aldehydes by hydrogen transfer from aqueous sodium formate catalyzed by [ RuCl2(TPPMS)2 2] provided unsaturated alcohols exclusively (Scheme 10.7). Addition of 3-CD shghtly inhibited the reaction [13]. It was speculated that this inhibition was probably due to complexation of the catalyst by inclusion of one of the non-sulfonated phenyl rings of the TPPMS ligand, however, no evidence was offered. 

Acrolein (CHj=CHCHO, also known as 2-propenal) is a a,P-unsaturated aldehyde that can be transformed reducfively to saturated or unsaturated alcohols by reduction of the C = 0 or C = C double bonds (Claus 1998). In addition, a,P-unsaturated aldehydes may undergo hydration reactions in aqueous solutions. It was observed that, under acidic (pH12) conditions, acrolein is hydrated to 3-hydroxypropanal (Jensen and Hashtroudi 1976). In a natural subsurface environment, where pH may range from 6.5 to 8.5, the hydration rate of acrolein increases with the pH and its half-life decreases. Based on an experiment to analyze effects of iron on acrolein transformation, Oh et al. (2006) note that, under acidic conditions (e.g., pH = 4.4), acrolein disappears rapidly from solution in the presence of elemental iron (Fig. 16.1). Moreover, the formation of... 

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